Transcript Document

S.I.S
Venoms For Humanity
S.I.S Shulov Innovative Science Ltd.
A biopharmaceutical company focused on
the discovery and development of novel
human therapeutics.
April 2013
1 Background
S.I.S Shulov Innovative Science Ltd. was
founded by the late Prof. Aharon Shulov
and Mr. Aviv Marx.
Prof. Aharon Shulov (1907-1997)
> Dept. of Zoology at the Hebrew University of
Jerusalem, Founder and General Manager of The
Jerusalem Biblical Zoo for over 40 years.
> Proposed a research program to identify the
analgesic components of snake venom
Mr. Aviv Marx
> Entrepreneur and family friend provides
funding.
2 Innovation
> Novel non-toxic short peptide has been
isolated from snake venom based on its
highly potent in-vivo analgesic activity
upon topical application
> Based on the above novel molecule a whole
family of related compounds
has
been
identified in various snake venoms
> One of the naturally occurring peptides
(coded Zep-4) and its chemically modified
version coded Zep-3, were chemically
synthesized in gram quantities.
> These
peptides
were
formulated
as
a
3 Intelectual Property
S.I.S has been granted a key patent in the
US which is in various stages of approval
worldwide
> US Patent - 7220725
Composition comprising an analgesic peptide and
therapeutic use thereof
>
As of March 2012, a new PTC patent
(#PCT/IL2012/050105)
was submitted
(U.S. application - # 61/468,212)
“Method for treating disorders of the skin” claiming
the therapeutic use of the peptides as a treatment
for viral induced clinical symptoms, such as HSV1
induced cold sores, HSV2 induced Genital Herpes and
Psoriasis.
4 Development Studies
>
Analytical and bio-analytical assays to trace the products
in buffers and in body fluids have been developed.
>
The % of trans-dermal permeability has been determined in a
Franz cell model
(permeability via pig’s ear skin is less than 0.1%)
>
Local Irritation Study is being performed
>
Local Sensitization study is being performed
>
Gynotoxicity studies are being performed
>
A mice model that mimics the clinical symptoms upon
infection with HSV1 is being established
>
Anti viral activity was established In- vitro and In- situ.
>
Determination of product stability
5 Current status of SIS's products
> S.I.S has conducted a large variety of
pre-clinical studies in accordance with the
requirements of the health regulatory
authorities and in order to support the
development processes of Zep-3 and Zep-4
cream as a product and to establish its
safety and efficacy.
> S.I.S has completed all essential
toxicology and safety studies required for
the submission of a file for Phase I
Clinical Study.
> Zep-3:, Zep -3 is in Phase I clinical
study (at the Dep. of Dermatology, Shiba
Hospital, Israel). After concluding the
study (Q2, 2013) we will initiate a Phase II
study for HSV1 Cold Sores indication and a
Phase II study for the Genital Herpes
indication.
6 Inhibition of HSV1 replication and
spreading in tissue culture
> The anti HSV1 activity of Zep-3 is determined
by measuring plaque forming, using tissue
culture vero cells in vitro.
> The results depicted below are representative
of one out of six repeated experiments
using two different batches of Zep - 3
>
>
Infected HSV1 treated with Zep-3 (4mg/ml or
8mg/ml)
Infected HSV1 treated with
peptide (4mg/ml or 8mg/ml).
“Scrambled”
> “Scrambled” refers to the identical amino
acids such as Zep-3 but in altered sequence
>
The anti-viral effect was produced without
causing Cell Toxicity in the Control Vero
Cells
7 Inhibition of HSV1
Replication by Zep-3
Zep – 3
(4mg/ml)
Zep – 3
(8mg/ml)
Scramble
(4mg/ml)
Scramble
(8mg/ml)
8 Zep-3 Inhibits Virus Replication
in tissue culture
> Zep-3 inhibits in dose dependent manner the
replication of HSV1 in Vero cells
Control - No
Peptide
Zep-3
9 Inhibition of HSV1 Replication by
Zep-3 in Organ Skin Culture
Control - None Infected
HSV1 – Infected + Scramble (8mg/ml)
HSV1 - Infected
HSV1 – Infected + ZEP-3 (8mg/ml)
10 Zep-4
for Treating Psoriasis
> Anecdotal data indicates that
Zep-4 upon topical application
is
efficient
for
treating
psoriasis in patients.
> Zep-4
relieves
redness.
itching
and
11 Safety and Toxicology
of Zep-3 and Zep-4
> Safety studies were carried out
in rats in which the following
end points were recorded:
body weight
Vitality
blood picture
Internal organs
histopathology
> No adverse side effects were
observed
at
twice
a
week
administration (topical or I.V.) of
high dosages for 200 days
12 Trans Dermal Permeability of Zep-3
and Zep-4
> Dermal Permeability was tested
using the ear-skin pig model.
> Zep-3 and Zep-4 show permeability
profile below 1% after 24 hrs.
> Significant amount of drug
accumulated in the skin.
13 HSV1 - The Market
> The total skin disorders market is estimated to be
$28 Billion annually (for 2011), about 1/3 of which is
due to viral infections, most of these being the
Herpes virus (HSV1, HSV2 and Herpes Zoster)
> By the age of 40, nearly 90% of adults, have been
exposed to HSV1, 15% of those exposed to HSV1 may
develop symptoms (blisters, cold sores) every year.
> In the Western World (U.S., Europe and Japan) the
potential market is over 100 Million patients, these
patients develop clinical symptoms every year.
14 HSV1 – The Market
(continue)
> Globally, about 4.0 billion people are estimated
to be infected with
Herpes Virus
> The incidence rate of cold sores, caused by the
HSV1 virus, is the
second largest worldwide,
trailing only behind common cold
> About 79% of the U.S. population is infected
with HSV1, with about
25-35% of the adults
enduring recurrent spate of cold Sores
> in recent years HSV1 has become the most common
cause of newly
diagnosed genital herpes
infections
”The need for innovative therapies for the
treatment of herpes simplex infection, and the
search for novel antiviral drugs
continues. This
presents a huge potential for the growth of herpes
15 HSV1 - The Market
>
(Contd.)
Above 40% of genital Herpes is caused by HSV1
and Zep-3 presents a possible prevention as
well as cure.
is- aMarket
chronic skin disease
16Psoriasis
Psoriasis
that is the most prevalent autoimmune
disease in the U.S., with as many as
7.5 million Americans affected (2.45%
of the population).
Psoriasis Market Info™ captures all the
relevant data on this disease. The
overall market value is $1.8+ billion
in 2010 in the U.S alone and $3.4
billion world-wide. This market is
expected to grow significantly in the
future, largely due to the chronic
nature of the disease, the high unmet
and
continued
need
for
topical
therapies which will make this market
approachable for any new therapy that
is both effective and safe.
17 Summary
of Zep-3
> Zep
-3
upon
topical
application
inhibits/prevents within less than 5
minutes the itching and pain induced by
Herpes
Simplex Virus Type I (HSV1)
and eliminates swelling and blister
formation in less than 36 hours
>
Zep – 3 inhibits in a dose dependent
manner the replication of HSV1 in Vero
cell line infected by the virus
> Zep-3,
demonstrates
analgesic
properties in acute and chronic
pain
animal models
18 Summary of Zep-4
> Zep-4
upon
topical
application
efficient for treating psoriasis
patients.
> Zep-4
relieves itching
associate with Psoriasis.
and
is
in
redness
19 Capital Requirements
Phase
Indicatio
n
Schedule
Phase I
Safety
Q1 (2013)
(2013)
-
Q2
0.4
Phase II
HSV1 Cold
Sores
Q3 (2013)
(2014)
-
Q4
1.6
Phase II
Genital
Herpes
Q1 (2014)
(2015)
- Q2
Phase I /
IIa
Psoriasis
Q1 (2014)
(2015
- Q2 ( 2.9
Cost
(M$)
2.3
20 Gant table
Task
Mode of Action
Long term
stability
Degradation
Pattern
ADME
Cost
(M$)
0.25
0.05
0.15
0.25
0.80
(Q2ׂ(2013) ---------------Q1
(2015((
---------+---------+-------+------------------------------------------------------------------------------------
Mucosal Tissue
Permeability &
Toxicity
0.05
Anti Viral
0.05
-------
----
21 History
Founded in 1985,
1985
-
S.I.S targeted the
development of
1989
-
innovative
pharmaceutical
1990
-
Viper venom is separated into
5
fractions
while
the
analgesic
activity
is
attributed to the fraction.
1992
-
The viper venom in the above
non toxic fraction was further
fractionated
on
a
size
exclusion
chromatography
column
S.I.S applies for first patent
based on viper venom following
the discovery of the analgesic
fraction.
products based on
properties
The
founding
of
S.I.S
pharmaceutical Ltd. by Prof
Aharon Shulov and Mr. Aviv
Marx.
Developing a pain model using
HCl for efficacy testing using
topical application.
of snake venom
1993
-
1996
-
S.I.S reveals the existence of
an uniform analgesic fraction
in three families of venomous
snakes.
22 History
1998 -
2000 -
2001 -
2002 -
S.I.S applies for a second
patent after discovering
that
the
analgesic
fraction is identified as
common, among all venomous
snakes.
The
structure
of
the
analgesic
peptides
was
identified chemically.
The
peptides
and
a
chemically
modified
version of one of them,
Zep,
were
chemically
synthesized and assessed
for
their
analgesic
activity relative to the
natural
snake
venom
derived molecules.
Third Patent is filed.
Composition comprising an
analgesic
peptide
(Zep)
and its therapeutic use.
Zep is successfully
formulated as cream and
tested to confirm its
efficacy.
2003
-
2007
2011
2011
-
2011
-
2012
-
2013
-
Conformation of the anti-pain
activity
in
various
in-vivo
animal
models
for
several
clinical indications.
Continuation
of
Pre-clinical
studies, validation of efficacy
in several animal models and
accumulating safety toxicology
data.
S.I.S focuses on the development
of one of its products for the
treatment
of
Herpes
Simplex
Virus (HSV1) induced symptoms,
such as Cold Sores, preventing
itching,
lesion
and
scab
formation.
A new patent was filed claiming
the efficacy of the product(s)
for
various
skin
disorders
including those induced by HSV1
infection.
Performing
safety
toxicology
studies for the submission of an
IND file for Phase I clinical
trial to the end of the year.
Phase I
Clinical Study.
23 Scientific Board
Prof. Israel Steiner (M.D.)
Head of Dep. of Neurology,
Beilinson Hospital Petach-Tikva,
Israel.
Head of Neurology Sciences Unit,
Hadassah
University
Hospital,
Jerusalem and a world expert in
molecular basis of HSV1 latency
and HSV1 infectivity.
Prof. Amos Panet
Dep. of Biochemistry and the
Chanock Center for Virology –
IMRIC,
the
Hebrew
University
Hadassah
Medical
School,
Jerusalem.
Prof.
Emeritus
of
Cancer
Research, Virus replication and
viral diseases, a world expert in
HSV1 molecular biology.
Dr. Avigdor Levanon
Executive
VP,
Business
Development and CTO at S.I.S
Formerly
VP,
Research
at
Prof. Elka Touito
Dep. of Pharmacy, the Hebrew
University
Hadassah
Medical
School, Jerusalem.
Head of Innovative Dermal, Trasdermal and
Transmucosal Delivery Group and a world
expert in enhancement of dermal drug
delivery for systemic action.
Prof. Yechiel Shai
Dep. of Biological Chemistry, The
Weizmann Institute of Science,
Rehovot, Israel
World expert in protein-membrane interaction
and protein-protein recognition within the cell
membrane
Dr. Naftali Primor
Executive
VP,
Research
and
Development at S.I.S.
Dr. Primor is a world renowned expert in the
toxicology and chemistry of snake venoms. He
has featured in the National Geographic Film
entitled "Snakes in The Holy Land", and is
constantly sought for his expertise and skills in the
24 Capital Requirements
Mr. Aviv Marx
President and CEO
Dr. Naftali
Primor
VP R&D
Tel: +972 (8) 931-4114
Mail: [email protected]
Tel: +972 (50) 536-3748
Mail: [email protected]
Dr. Avigdor Levanon
Executive VP,
Business Development
Tel: +972 (50) 536-3748
Mail: [email protected]
THANK
YOU
April
2013
S.I.S Shulov Innovative
S c i e n c e
L t d .
Venoms For
Humanity